A systematic approach for scalable purification of virus-like particles

Virus-like particles (VLPs) are increasingly recognized as promising vaccine candidates and drug-delivery platforms because they do not contain genetic materials, mimic viral structures, and possess strong antigenic properties. Various hosts, including microorganisms, yeast, and insect cells, are commonly used for VLP expression. Recently, silkworms have emerged as a significant host for producing VLPs, providing a cost-effective and straightforward approach for large-scale expression. Despite the progress in VLP expression technology, purification methods for VLPs are still in their infancy and often rely on unscalable ultracentrifugation techniques. Moreover, VLP purification represents a substantial portion of the overall production cost, highlighting the urgent need for efficient and scalable downstream processing methods to overcome the current challenges in VLP production. Considering their differing structures and properties, this review systematically summarizes the published results of scalable downstream processes for both enveloped and non-enveloped VLPs. Its aim is to provide a comprehensive overview and significantly contribute to developing future VLP production for pharmaceutical applications, thereby guiding and inspiring further research in this field.